Synthesis and antimalarial activity of new analogues of amodiaquine

Recent developments in the design and synthesis of hybrid molecules basedon aminoquinoline ring and their antiplasmodial evaluation

“…Related 4-anilinoquinolines bearing other amino groups in aryl moiety of AQ were prepared recently, using analogous synthetic strategy [161,162]. These structural modifications demonstrated a decrease of the cytotoxicity and an increase in selectivity index that justifies further synthetic works.…”

4-Aminoquinoline derivatives: Synthesis, in vitro and in vivo antiplasmodial activity against chloroquine-resistant parasites

“…On careful examination of the structure of amodiaquine, we have found that there is still some scope for modification of basic scaffolds to improve antimalarial activity. In this way newer cost effective compounds with significant antimalarial activity can be designed and synthesized.Till now little systematic study has been carried out using different electron releasing and donating groups on phenyl rings which exhibited the effect of substituents on the activity of the basic scaffold [14]. Keeping these facts in mind and in the continuation of our ongoing projects on malaria drug discovery [15][16][17][18] and biophysical analysis of amodiaquine analogues [19], we have synthesized and characterized two different libraries of small 4-aminoquinoline analogues under series I & II as shown in Figure 2.…”

Synthesis, β-hematin inhibition studies and antimalarial evaluation of dehydroxy isotebuquine derivatives against Plasmodium berghei

“…Blocking of bioactivation pathways by removal of the phenolic group or introduction of non reactive substituents has been the main strategy. 5,[12][13][14] From SAR studies it has been found that in the amodiaquine and tebuquine 3 series of 4-aminoquinoline analogs, the presence of the 4 0 -hydroxy group within the aromatic ring imparts greater inherent antimalarial activity against chloroquine resistant parasites than the corresponding dehydroxy analogs. 5 Interchange of the hydroxy group and the Mannich side chain provides a means of preventing oxidation to toxic metabolites while retaining possible important bonding interactions with the aromatic hydroxyl function generated an amodiaquine regioisomer called isoquine 4 which cannot form toxic metabolites by simple oxidation and is potent against chloroquine resistant parasites …”